A widely used aromatase inhibitor, letrozole, has shown clinically meaningful improvements in sperm concentration categories among men with severe infertility, according to a new randomised clinical trial.
Researchers investigated whether letrozole could improve semen-based outcomes in men with spermatogenic failure (SPGF), a severe form of male infertility that includes non-obstructive azoospermia, cryptozoospermia and severe oligozoospermia. Current treatment options for these patients remain limited, with many ultimately requiring assisted reproductive techniques.
The multicentre study recruited 296 men from 10 infertility centres in China between July 2023 and March 2024. Participants had a mean age of 30.2 years and were randomly assigned to receive either letrozole (2.5 mg daily) plus vitamins C and E, or vitamins C and E alone as a control intervention. Treatment lasted three months.
Results
The primary outcome was improvement in World Health Organization sperm concentration categories. At three months, 14.3% of men in the letrozole group achieved an upgrade in sperm concentration category compared with 5.4% in the control group, representing a statistically significant difference.
Letrozole-treated participants were also more likely to achieve a higher overall sperm concentration grade, with improved odds compared with controls. In addition, secondary outcomes showed higher rates of improvement in total motile sperm count categories and favourable hormonal changes, including increased testosterone and gonadotropin levels and reduced estradiol.
However, improvements in raw semen parameters were not significantly different between groups. The treatment was generally well tolerated, although reduced libido was reported more frequently in the letrozole group (12.2% vs 5.4%).
The findings suggest that letrozole may offer a useful medical option to “downstage” severity in male infertility, potentially increasing the chances of success with less invasive reproductive approaches. However, the authors note that benefits were primarily seen in categorical sperm improvements rather than absolute semen parameter changes.
Further research is needed to determine whether these improvements translate into higher natural conception or assisted reproduction success rates, and to clarify long-term safety and optimal patient selection.
Reference
Sun Y et al. Letrozole and infertility among males with spermatogenic failure: a randomized clinical trial.
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